The specific aims of this project are to evaluate sex-steroid levels and prostate specific antigen levels in men with and without prostate cancer. It is believed that sex-steroids play a role in development of prostate cancer, and ind inhibition of testosterone action is being targeted as an approach to prostate cancer prevention. Longitudinal measurements of sex-steroids before development of prostate cancer could provide further insight regarding the role of these hormones as risk factors for development of prostate cancer. Prostate specific antigen (PSA) has been found to be a valuable marker for assessing the risk of prostate cancer presence in men. The optimal method for using this marker in prostate cancer screening has not been determined. Routine use of PSA for prostate cancer detection is associated with large numbers of false positive tests (low specificity), and is the source of great controversy regarding the use of PSA. Low specificity among men without prostate cancer results in tremendous cost in terms of unnecessary testing. Longitudinal study of PSA has provided insight into the changes that occur in PSA prior to prostate cancer diagnosis. As a result it is now known that: 1) PSA changes are more rapid in men with prostate cancer compared to men without prostate cancer; and, 2) rate of change in PSA as a criterion velocity as an early marker for prostate cancer has the potential to decrease unnecessary testing of those men with PSA elevations who do not have prostate cancer. Further evaluation of longitudinal PSA measurements is needed in order to apply rate of change in PSA (PSA velocity) to prostate cancer screening, and to determine the safety of following men using PSA velocity (as opposed to biopsy of all men with PSA elevations). Furthermore, longitudinal measurements of different molecular forms of PSA (free and bound PSA) may provide an improved means of identifying men with prostate cancer since it has been shown that men with prostate cancer have a higher percentage of bound PSA in sera. The proposed project will be conducted in conjunction with investigators at The Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing prospective aging study of the National Institute of Aging (NIA) which has enrolled approximately 1500 male participants since 1958. Active participants return every 2 years for evaluation and frozen sera is available for active and inactive participants at 2 year intervals. Available stored sera will be used to measure sex-steroids and PSA (retrospective studies). Digital rectal examination and serum analysis of active BLSA participants will be ongoing (prospective studies). Data will be evaluated longitudinally with respect to participant diagnosis.